Clinical and neurodevelopmental predictors of psychotic disorders in children and adolescents at clinical high risk for psychosis: the CAPRIS study.

BACKGROUND: The neurodevelopmental hypothesis of schizophrenia represents the disorder as an expression of an alteration during the brain development process early in life. Neurodevelopmental variables could become a trait marker, and the study of these variables in children and adolescents at clinical high risk for psychosis (CHR) could identify a specific cluster of patients who later developed psychosis. The aim of this study is to describe clinical and neurodevelopment predictors of transition to psychosis in child and adolescent participants at CHR. Naturalistic longitudinal two-center study of 101 CHR and 110 healthy controls (HC) aged 10-17. CHR participants were children and adolescents aged 10-17, meeting one or more of the CHR criteria assessed at baseline and at 18 months' follow-up. Neurodevelopmental variables assessed were obstetric complications, delay in principal development milestones, and presence of a neurodevelopment diagnosis. Pairwise comparisons, linear regressions, and binary logistic regression were performed.A transition rate of 23.3% at 1.5 years was observed. Participants who developed psychosis (CHR-P) showed higher rates of grandiosity and higher proportions of antipsychotic medication intake at baseline compared to participants who did not develop a psychotic disorder (CHR-NP). In terms of neurodevelopment alterations, CHR-P group showed a higher proportion of participants reporting delay in language development than the CHR-NP and HC groups. The odds of psychosis increased by 6.238 CI 95% [1.276-30.492] for a one-unit increase in having a positive score in grandiosity; they increased by 4.257 95% CI [1.293-14.023] for a one-unit increase in taking antipsychotic medication, and by 4.522 95% [1.185-64.180] for showing language development delay. However, the p-values did not reach significance after adjusting for multiple comparisons.A combination of clinical and neurodevelopmental alterations could help predict the transition to psychotic disorder in a CHR child and adolescent sample. Our results suggest the potential utility of collecting information about neurodevelopment and using these variable multifactorial models to predict psychosis disorders.

Cognitive reserve and its correlates in child and adolescent offspring of patients diagnosed with schizophrenia or bipolar disorder.

AIM: To analyze cognitive reserve (CR) in child and adolescent offspring of patients diagnosed with schizophrenia (SZ-off) or bipolar disorder (BD-off) and compare them with a group of community controls (CC-off). We also aimed to investigate whether there was an association between CR and clinical and neuropsychological variables according to group. METHODS: The study included 46 SZ-off, 105 BD-off and 102 CC-off. All participants completed assessments regarding CR and clinical, neuropsychological and psychosocial functioning. CR was measured with a proxy based on premorbid intelligence, parental occupational level, educational attainment, developmental milestones and sociability. The clinical assessment included the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime, the Semi-structured Interview for Prodromal Syndromes, and the Global Assessment Functioning scale. The neuropsychological assessment included measures of executive functioning, attention, verbal memory, working memory and processing speed. RESULTS: SZ-off showed a lower level of CR compared to BD-off and CC-off, while BD-off showed an intermediate level of CR between SZ-off and CC-off. Moreover, an association between higher CR and less lifetime psychopathology, fewer prodromal psychotic symptoms, higher psychosocial functioning, and a higher working memory score was observed in all groups, but it was stronger in SZ-off. CONCLUSIONS: CR seemed to be associated with psychopathology, clinical symptoms, psychosocial functioning, and some cognitive functions. SZ-off appeared to benefit more from a higher CR, therefore it could be considered a protective factor against the development of clinical symptomatology and cognitive impairment.

Age-related change in cortical thickness in adolescents at clinical high risk for psychosis: a longitudinal study.

Progression to psychosis has been associated with increased cortical thinning in the frontal, temporal and parietal lobes in individuals at clinical high risk for the disorder (CHR-P). The timing and spatial extent of these changes are thought to be influenced by age. However, most evidence so far stems from adult samples. Longitudinal studies are essential to understanding the neuroanatomical changes associated to transition to psychosis during adolescence, and their relationship with age. We conducted a longitudinal, multisite study including adolescents at CHR-P and healthy controls (HC), aged 10-17 years. Structural images were acquired at baseline and at 18-month follow-up. Images were processed with the longitudinal pipeline in FreeSurfer. We used a longitudinal two-stage model to compute the regional cortical thickness (CT) change, and analyze between-group differences controlling for age, sex and scan, and corrected for multiple comparisons. Linear regression was used to study the effect of age at baseline. A total of 103 individuals (49 CHR-P and 54 HC) were included in the analysis. During follow-up, the 13 CHR-P participants who transitioned to psychosis exhibited greater CT decrease over time in the right parietal cortex compared to those who did not transition to psychosis and to HC. Age at baseline correlated with longitudinal changes in CT, with younger individuals showing greater cortical thinning in this region. The emergence of psychosis during early adolescence may have an impact on typical neuromaturational processes. This study provides new insights on the cortical changes taking place prior to illness onset.

Psychopathology and mental health service use among youth in foster care admitted to a psychiatric inpatient unit: a 4-year retrospective controlled study.

Youth in foster care (FC) are at increased risk of poor psychosocial outcomes. The aim of this study was to assess psychopathology and mental health service use among youth living in FC who require psychiatric hospitalisation. All individuals admitted to our Children and Adolescent Inpatient Psychiatry Unit between 2014 and 2017 who were in FC were systematically reviewed. The control group was defined as all youth living with their immediate family and hospitalised in our unit throughout 2016. We identified 89 patients placed in FC and 247 controls. Socio-demographic and clinical data were retrospectively collected from computerised charts. A survival analysis of emergency department visits and readmission to the hospital was conducted. Compared to controls, the FC group presented significantly higher rates of conduct disorder (78.7% vs 14.6%; p < 0.001) and substance use disorder (49.4% vs 27.5%; p < 0.001), mainly cannabis use (34.8% vs 16.6%; p < 0.001); higher rates of comorbidity (96.6% vs 55.9%; p < 0.001) and mean number of comorbid diagnoses (3.3 ± 1.1 vs 2.3 ± 0.5; p < 0.001). The FC group had a higher number of emergency room visits before and after admission than controls. FC youth were also 2.77 times more likely to visit the emergency department after discharge, and in a shorter time period, than controls (p = 0.004). Disruptive behaviours, substance use disorder, and comorbid psychopathology were all more prevalent among FC youth than controls. Specific strategies are needed to optimize community mental health resources and address the increased use of emergency services by these youth before and after hospitalisation.

Brain structural trajectories in youth at familial risk for schizophrenia or bipolar disorder according to development of psychosis spectrum symptoms.

BACKGROUND: The evaluation of child and adolescent offspring of patients with schizophrenia (SzO) or bipolar disorder (BpO) may help understand changes taking place in the brain in individuals at heightened risk for disease during a key developmental period. METHODS: One hundred twenty-eight individuals (33 SzO and 46 BpO, considered jointly as 'Familial High Risk' (FHR), and 49 controls) aged 6-17 years underwent clinical, cognitive and neuroimaging assessment at baseline, 2- and 4-year follow-up. Twenty FHR participants (11 SzO and 9 BpO) developed psychotic spectrum symptoms during follow-up, while 59 FHR participants did not. Magnetic resonance imaging was performed on a 3Tesla scanner; cortical surface reconstruction was applied to measure cortical thickness, surface area and grey matter volume. RESULTS: FHR participants who developed psychotic spectrum symptoms over time showed greater time-related mean cortical thinning than those who did not and than controls. By subgroups, this effect was present in both BpO and SzO in the occipital cortex. At baseline, FHR participants who developed psychotic spectrum symptoms over time had smaller total surface area and grey matter volume than those who did not and than controls. Over time, all FHR participants showed less longitudinal decrease in surface area than controls. In those who developed psychotic spectrum symptoms over time, this effect was driven by BpO, while in those who did not, this was due to SzO, who also showed less grey matter volume reduction. CONCLUSION: The emergence of psychotic spectrum symptoms in FHR was indexed by smaller cross-sectional surface area and progressive cortical thinning. Relative preservation of surface area over time may signal different processes according to familial risk. These findings lay the foundation for future studies aimed at stratification of FHR youth.

Cognitive reserve in patients with first-episode psychosis as outcome predictor at 5-year follow-up.

Cognitive reserve (CR) is the premorbid brain capacity to cope with neural damage. People with good CR can tolerate higher levels of pathological brain injuries before displaying clinical symptoms than others. This study aimed to analyze CR in a sample of patients diagnosed with first-episode psychosis (FEP) during childhood or adolescence, comparing them to a community control group (CC) and assessing the predictive value of CR regarding psychosocial functioning, clinical symptoms and neuropsychological variables at the 5-year follow-up. 57 patients diagnosed with FEP during childhood or adolescence and 37 controls completed clinical, neuropsychological, and psychosocial functioning assessments at baseline and 5-year follow-up. CR was assessed in both groups at baseline. The FEP group showed lower CR scores than the CC group. Higher CR in the FEP group was associated with fewer psychotic negative symptoms, total psychotic symptoms and depressive symptoms, higher psychosocial functioning, and less impaired memory and attention at the 5-year follow-up. CR is associated with long-term clinical, neuropsychological and psychosocial functioning outcomes in patients diagnosed with FEP during childhood or adolescence.

Hospital Admission for Severe Pediatric Dissociative Disorder.

Although children with dissociative disorders (DD) are referred to mental health inpatient units, no research exists to endorse this. We studied the outcomes of patients with DD over a 5-year period on a national inpatient unit for children up to 12 years of age. Demographic, clinical, and satisfaction data were collected and compared with the data of other inpatients not having DD. Eight patients were identified, of whom six were female. All had several comorbidities. Mean Children's Global Assessment Scale scores improved from admission to discharge (from 31 to 61, respectively). Admissions in DD were longer by 53 days (p = 0.059), and parents were statistically less satisfied about professionals' ability to listen to worries they may have about their child (p = 0.049). Referrers should expect children with DD to respond as well to inpatient interventions as those with other diagnoses but potentially with marginally longer admissions and lower parental satisfaction.

Shared psychotic disorder in children and young people: a systematic review.

This study aimed at searching the literature and reassessing the concept of shared psychotic disorder (SPD) in young people under 18 taking into account genetic vulnerability, social circumstances and family situation to have a better understanding of this condition. Published case reports from 1980 through to March 2017, which included children and adolescents meeting DSM-III/IV/IV-TR or ICD 10 criteria of SPD, were identified. Sociodemographic and clinical variables were collected and analysed; a post hoc analysis comparing inductors and induced was also conducted. Four hundred and eight articles were assessed for eligibility of which 27 were included in the qualitative and quantitative synthesis. Thirty families were described. Forty-eight children were identified including 6 inductors and 42 induced. Although delusional beliefs were presented in all subjects, hallucinations were only reported in 50% of the inductors and 27% of the inductees. Social isolation was the most common social context (83.3% of the inductors; 76.2% of the induced) and 18 out of 45 children (data missing for n = 3) were initially separated from adults involved although the outcome of the symptoms was not different from those who were not separated. Children who were inductors were more likely to meet criteria of major psychotic illness in the future. Most of the induced children involved in a case of shared psychosis were first-degree relatives of the inductor. Shared psychotic disorder probably occurs in premorbid predisposed individuals where genetic and environmental factors play an important role in the development of the psychotic episode.

Motivational interviewing for smoking cessation in a psychiatric day hospital: a feasibility study.

OBJECTIVE: Our main objective was to test the feasibility of adding motivational interviewing to the usual smoking cessation treatment for patients with psychiatric disorders attending a day hospital. METHODS: A total of 44 patients participated in the study: a comparison group of 25 patients, all of whom received the usual smoking cessation treatment (nicotine replacement therapy, 1 hour of weekly group therapy, and daily individual advice), and an intervention group of 19 patients who received the usual smoking cessation treatment plus up to four motivational interviewing sessions. Data included sociodemographics, psychiatric diagnosis, cigarette use, and engagement in treatment. Descriptive analyses were conducted, along with logistic regression to test for differences on abstinence and daily smoking rates. RESULTS: All 19 patients offered the motivational interviewing accepted it, and all of them completed at least one session (M = 2.53, SD = 0.234, Range = 1 to 4). At the end of treatment, four patients in the intervention group were abstinent (versus none in the comparison group), but this was not statistically significant. Both groups showed a mean daily reduction of eight cigarettes. After introducing all variables into the regression models, none reached significance. CONCLUSIONS: Adding motivational interviewing to usual smoking cessation treatment in a psychiatric day hospital seems feasible and acceptable. Further, more rigorous research is needed.

Altered Temporal Dynamics of Resting-State Functional Magnetic Resonance Imaging in Adolescent-Onset First-Episode Psychosis.

BACKGROUND: Dynamic functional connectivity (dFC) alterations have been reported in patients with adult-onset and chronic psychosis. We sought to examine whether such abnormalities were also observed in patients with first episode, adolescent-onset psychosis (AOP), in order to rule out potential effects of chronicity and protracted antipsychotic treatment exposure. AOP has been suggested to have less diagnostic specificity compared to psychosis with onset in adulthood and occurs during a period of neurodevelopmental changes in brain functional connections. STUDY DESIGN: Seventy-nine patients with first episode, AOP (36 patients with schizophrenia-spectrum disorder, SSD; and 43 with affective psychotic disorder, AF) and 54 healthy controls (HC), aged 10 to 17 years were included. Participants underwent clinical and cognitive assessments and resting-state functional magnetic resonance imaging. Graph-based measures were used to analyze temporal trajectories of dFC, which were compared between patients with SSD, AF, and HC. Within patients, we also tested associations between dFC parameters and clinical variables. STUDY RESULTS: Patients with SSD temporally visited the different connectivity states in a less efficient way (reduced global efficiency), visiting fewer nodes (larger temporal modularity, and increased immobility), with a reduction in the metabolic expenditure (cost and leap size), relative to AF and HC (effect sizes: Cohen's D, ranging 0.54 to.91). In youth with AF, these parameters did not differ compared to HC. Connectivity measures were not associated with clinical severity, intelligence, cannabis use, or dose of antipsychotic medication. CONCLUSIONS: dFC measures hold potential towards the development of brain-based biomarkers characterizing adolescent-onset SSD.

Sex Differences in Serum Prolactin Levels in Children and Adolescents on Antipsychotics: A Systematic Review and Meta-Analysis.

BACKGROUND: Serum prolactin levels are influenced by sex, physical development and medications among other factors. Antipsychotics usually increase serum prolactin levels in both adults and younger patients, but no study has reviewed the potential association between sex and vulnerability for developing hyperprolactinemia among children and adolescents. OBJECTIVE: Systematic review and meta-analysis of serum prolactin levels in children and adolescents on antipsychotic treatment for any psychiatric diagnosis to determine the effect of sex. METHODS: A systematic search was performed in MEDLINE/PubMed/Web of Science and Cochrane databases for randomized controlled trials of antipsychotics in children and adolescents reporting serum prolactin levels by sex. RESULTS: Of 1278 identified records, seven studies were included, comparing different single antipsychotics to placebo (risperidone N=4; lurasidone N=1; olanzapine N=1; queriapine N=1). Both male and female children and adolescents on antipsychotics presented a significant increase in prolactin levels relative to subjects receiving a placebo. (Male: 16.53 with 95% CI: 6.15-26.92; Female: 26.97 with 95% CI: 9.18-44.75). The four studies using risperidone had similar findings (Male: 26.49 with 95% CI: 17.55-35.43; Female: 37.72 with 95% CI: 9.41-66.03). In the direct comparison between sexes, females showed greater increases in prolactin, but the differences were not statistically significant. CONCLUSION: Serum prolactin levels are increased in children and adolescents of both sexes on antipsychotics, with females showing a slightly greater increase than males. Further research is needed to clarify the influence of sex and pubertal status on prolactin levels in children and adolescents taking antipsychotics.

What Role for Long-Acting Injectable Antipsychotics in Managing Schizophrenia Spectrum Disorders in Children and Adolescents? A Systematic Review.

BACKGROUND: Long-acting injectable antipsychotics (LAIAs) are an efficacious and well-tolerated treatment in adults with schizophrenia spectrum disorders (SSD). However, there is less evidence for their use in children and adolescents. OBJECTIVES: The aim of this systematic review was to summarize findings regarding the effectiveness and side effects of LAIA in children and adolescents with SSD. METHODS: Four databases (Web of Science, PubMed, MEDES, and Dialnet) were systematically searched for articles published between inception and 12 March, 2022, with the following inclusion criteria: (1) original articles or case reports; (2) providing data on efficacy/effectiveness or safety/tolerability of LAIA treatment in children and adolescents diagnosed with SSD (schizophrenia, schizoaffective disorder, schizophreniform disorder, non-affective psychotic disorder); (3) mean age of samples ≤ 18 years; and (4) written in English or Spanish. Exclusion criteria were review articles, clinical guides, expert consensus as well as posters or oral communication in conferences. The risk of bias was assessed using the ROBIS tool. RESULTS: From 847 articles found, 13 met the inclusion criteria. These included seven single case reports or case series, four retrospective chart reviews, a 24-week open-label trial, and one observational prospective study, covering a total of 119 adolescents (aged 12-17 years) with SSD. Almost all the articles described data on second-generation LAIA (53 patients on risperidone [once every other week], 33 on paliperidone palmitate [once monthly], 10 on aripiprazole [once monthly], and two on olanzapine pamoate [once monthly]). Twenty-one patients were reported to be only on first-generation LAIAs. Non-adherence was the main reason for starting an LAIA. In all of the studies, the use of LAIAs was associated with improvement in the patients' symptoms. CONCLUSIONS: There are few studies assessing the use of LAIAs in adolescents with SSD. Overall, these treatments have suggested good effectiveness and acceptable safety and tolerability. However, we found no studies examining their use in children aged < 12 years. The problems and benefits linked to this type of antipsychotic formulation in the child and adolescent population require further study, ideally with prospective, controlled designs.

Longitudinal Changes in Cortical Surface Area Associated With Transition to Psychosis in Adolescents at Clinical High Risk for the Disease.

OBJECTIVE: Identifying biomarkers of transition to psychosis in individuals at clinical high risk for psychosis (CHR-P) is essential to understanding the mechanisms underlying the disease. Although cross-sectional abnormalities in cortical surface area (CSA) have been demonstrated in individuals at CHR-P who transition to psychosis (CHR-P-T) compared with those who do not (CHR-P-NT), how CSA longitudinally develops remains unclear, especially in younger individuals. We set out to compare CSA in adolescents at CHR-P and healthy controls (HC) over 2 points in time. METHOD: A longitudinal multicenter study was performed in adolescents at CHR-P in comparison to HC and according to transition to psychosis. Magnetic resonance imaging scans were acquired at baseline, at 18-month follow-up, or at the time of transition. Images were pre-processed and hemisphere and regional CSA were computed using FreeSurfer. Between-group analyses were performed with linear mixed-effects models. RESULTS: A total of 313 scans (107 CHR-P and 102 HC) were included in the analysis. At 18 months, the rate of transition to psychosis in CHR-P was 23.4%. Adolescents at CHR-P-T presented greater age-related decrease in CSA in the left parietal and occipital lobes compared with HC, and in the bilateral parietal lobe and right frontal lobe relative to CHR-P-NT. These results were not influenced by antipsychotic treatment, cannabis use, or intelligence quotient (IQ). CONCLUSION: Adolescents at CHR-P that developed a psychotic disorder presented different developmental trajectories of CSA relative to those who did not. A relatively greater decrease in CSA in the parietal and frontal lobes may index clinical transition to psychosis in adolescents at CHR-P.

Obsessive-Compulsive Spectrum Symptoms Are Associated With Functional Impairment in Children and Adolescents With Psychosis Risk Syndrome: The CAPRIS Study.

Objective: To compare clinical and functional variables among 3 groups of children and adolescents: subjects at clinical high risk for psychosis (CHR-P) who also have obsessive-compulsive symptoms (OCS), CHR-P patients without OCS, and healthy controls (HC).Methods: A total of 128 CHR-P patients and 98 HC between the ages of 10 and 17 years were recruited as part of a multicenter prospective longitudinal study conducted in Spain between January 1, 2011, and December 31, 2018, with diagnoses made for CHR-P using the Scale of Prodromal Symptoms (SOPS). Two groups were obtained based on Leyton Obsessional Inventory-Child Version (LOI-CV) scores: 64 CHR-P patients with OCS (OCS+) and 64 CHR-P patients without OCS (OCS-). Clinical variables were analyzed with a generalized linear model.Results: Overall, 128 CHR-P patients, 64 (50%) with OCS (mean ± SD age = 15.5 ± 1.4 years, 34.4% male), 64 CHR-P patients without OCS (mean ± SD age = 15.1 ± 1.9 years, 34.4% male), and 98 HC (mean ± SD age = 15.5 ± 1.5 years, 42.9% male), of whom 19 (19.5%) had OCS, were included. Generalized linear model analysis revealed significant differences between the groups. The OCS+ group showed more severe prodromal symptoms (P = .007), worse functioning at baseline (P = .044) and during the previous year (P = .004), and more dysmorphophobic symptoms (P < .001) compared to the OCS- group. OCS+ patients were also more frequently treated with antidepressants (P = .004) than were OCS- patients.Conclusions: In our sample, among children and adolescents with CHR-P, the prevalence of OCS was high (50%). OCS+ subjects had a more severe clinical and functional profile than OCS- subjects. Early detection and treatment of these symptoms can lead to better outcomes for these patients.

Genetic and Structural Brain Correlates of Cognitive Subtypes Across Youth at Family Risk for Schizophrenia and Bipolar Disorder.

OBJECTIVE: Cognitive impairment is an important feature of schizophrenia (SZ) and bipolar disorder (BP) with severity across the two disorders characterized by significant heterogeneity. Youth at family risk for SZ and BP were clustered based on cognitive function and examined in terms of the clinical, genetic, and brain imaging correlates of cluster membership. METHOD: One hundred sixty participants, 32 offspring of patients with SZ, 59 offspring of patients with BP and 69 offspring of healthy control parents underwent clinical and cognitive assessments, genotyping and structural MRI. K-means clustering was used to group family risk participants based on cognitive measures. Clusters were compared in terms of cortical and subcortical brain measures as well as polygenic risk scores. RESULTS: Participants were grouped in 3 clusters with intact, intermediate, and impaired cognitive performance. The intermediate and impaired clusters had lower total brain surface area compared with the intact cluster, with prominent localization in frontal and temporal cortices. No between-cluster differences were identified in cortical thickness and subcortical brain volumes. The impaired cluster also had poorer psychosocial functioning and worse PRS-COG compared with the other 2 clusters and with offspring of healthy control parents, while there was no significant between-cluster difference in terms of PRS-SZ and PRS-BP. PRS-COG predicted psychosocial functioning, yet this effect did not appear to be mediated by an effect of PRS-COG on brain area. CONCLUSION: Stratification based on cognition may help to elucidate the biological underpinnings of cognitive heterogeneity across SZ and BP risk.

Radiological findings in brain MRI scans in youth with early-onset psychosis: A controlled study.

There is a lack of consensus on whether routine brain magnetic resonance imaging (MRI) should be recommended as part of the initial assessment in patients with psychosis. No study so far has qualitatively assessed brain MRI in patients with early-onset psychosis (EOP), in whom neurodevelopmental factors may play a stronger role. We aimed to determine the prevalence of brain MRI findings in patients with EOP compared to healthy controls, and assess whether these findings were clinically relevant. Retrospective clinical chart review of all patients with EOP in whom a brain MRI scan was acquired during admission to an inpatient child and adolescent psychiatry unit during January 2013-December 2017, compared to age and biologically assigned gender matched healthy controls. Between group analyses tested differences in rates of qualitatively abnormal MRI scans and changes in clinical management as a result of radiological findings. A total of 256 individuals were included (128 patients with EOP and 128 healthy controls). Patients with EOP presented with a significantly higher rate of abnormal MRI scans relative to healthy controls (21.9% vs 11.7%, p = .030; OR = 2.11, [95% CI:1.06-4.17]). Radiological findings in the EOP group triggered clinical referral for further evaluation or management more often than in the healthy control group (7.0% vs 1.6%, p = .030; OR = 4.76, [95% CI:1.01-22.50]). MRI scans in youth with EOP may be characterized by an increased number of radiological abnormalities than in controls. The rates of MRI findings requiring clinical referral suggests that routine MRI acquisition may need to be considered in patients with EOP.

Theory of mind performance and prefrontal connectivity in adolescents at clinical high risk for psychosis.

Theory of mind(ToM) impairment is a key feature of psychotic disorders and has been documented in individuals at clinical high-risk for psychosis (CHR), suggesting that it may predate illness onset. However, no study to date has examined brain functional correlates of ToM in individuals at CHR during adolescence. The "Reading-the-Mind-in-the-Eyes" test was used to measure ToM performance in 50 CHR youth, 15 of whom transitioned to psychosis (CHR-t) at follow-up (12 ± 6 months) and 36 healthy volunteers. Resting-state functional MRI was acquired to evaluate functional connectivity within the default mode network. Group by age interaction revealed an age-positive association in ToM performance in healthy volunteers, which was not present in adolescents at CHR-t. Intrinsic functional connectivity in the medial prefrontal cortex was reduced in adolescents at CHR-t relative to those who did not transition and to healthy volunteers. Survival analyses revealed that participants at CHR with lower medial prefrontal cortex connectivity were at greatest risk of developing psychosis at follow-up. We demonstrate that lack of age-related maturation of ToM and reduced medial prefrontal cortex connectivity both precede the onset of psychosis during adolescence. Medial prefrontal cortex connectivity holds potential as a brain-based marker for the early identification of transition to psychosis.

Cognitive heterogeneity in the offspring of patients with schizophrenia or bipolar disorder: a cluster analysis across family risk.

BACKGROUND: Neurocognitive impairment is considered to lie on a continuum of severity across schizophrenia (SZ) and bipolar disorder (BP), possibly reflecting a gradient of neurodevelopmental load. Cluster analyses have identified different levels of impairment across the two disorders, from none to widespread and severe. We for the first time used this approach to examine cognitive function pooling together children and adolescents at familial risk of SZ or BP. METHODS: 220 participants, 49 offspring of individuals with schizophrenia (SZO), 90 offspring of individuals with bipolar disorder (BPO) and 81 offspring of healthy control parents (HC), aged 6 to 17 years, underwent a comprehensive clinical and cognitive assessment. Cognitive measures were used to group SZO and BPO using K-means clustering. Cognitive performance within each of the clusters was compared to that of HC and clinical variables were compared between clusters. RESULTS: We identified three cognitive subgroups: a moderate impairment group, a mild impairment group, and a cognitively intact group. Both SZO and BPO were represented in each of the clusters, yet not evenly, with a larger proportion of the SZO in the moderately impaired cluster, but also a subgroup of BPO showing moderate cognitive dysfunction. LIMITATIONS: Participants have yet to reach the age of onset for the examined disorders. CONCLUSIONS: The findings point to a range of neurodevelopmental loadings across youth at familial risk of both SZ and BP. They have therefore important implications for the stratification of cognitive functioning and the possibility to tailor interventions to individual levels of impairment.

Neural Correlates of Theory of Mind in Autism Spectrum Disorder, Attention-Deficit/Hyperactivity Disorder, and the Comorbid Condition.

Theory of mind (ToM) or mentalizing difficulties is reported in attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), but the mechanism underpinning these apparently shared deficits is relatively unknown. Eighty-three young adult males, 19 with ASD alone, 21 with ADHD alone, 18 with dual diagnosis of ASD and ADHD, and 25 typically developing (TD) controls completed the functional magnetic resonance imaging version of the Frith-Happé animated-triangle ToM task. We compared neural function during ToM with two non-ToM conditions, random and goal directed motions, using whole-brain and region-of-interest analysis of brain activation and functional connectivity analyses. The groups showed comparable ToM task performance. All three clinical groups lacked local connectivity increase shown by TD controls during ToM in the right temporoparietal cortex, a key mentalizing region, with a differentially increased activation pattern in both ASD and comorbid groups relative to ADHD. Both ASD groups also showed reduced connectivity between right inferior lateral prefrontal and posterior cingulate cortices that could reflect an atypical information transmission to the mentalizing network. In contrast, with mentalizing both ADHD groups showed decreasing connectivity between the medial prefrontal and left temporoparietal cortices when compared to TD controls. Therefore, despite the complex pattern of atypical brain function underpinning ToM across the three disorders, some neurofunctional abnormalities during ToM are associated with ASD and appeared differentiable from those associated with ADHD, with the comorbid group displaying combined abnormalities found in each condition.